Studies on the inhibition of neuronal uptake of catecholamines is proposed in which reversible and irreversible inhibitors are used. The biochemical consequences of this inhibition will be examined by determining changes in the efflux and metabolism of the catecholamine and by determining the extent of irreversible binding. The studies will be conducted in rabbit aorta and in rat brain. The uptake and metabolism of norepinephrine-3H is monitored in aorta by examining tissue and incubation bath after a 60-minute exposure period. Accumulation by brain tissue is measured in a synaptosome enriched preparation after a short (3-5 minute) incubation with catecholamine. These techniques have been used to examine the sites of action of compounds that cause a decrease in net accumulation of norepinephrine-3H, and the details of this decrease such as changes in storage and metabolism will be investigated.